Resistance to beta-lactam antibiotics is wide spread and a key concern. One of the mechanisms bacteria have developed against beta-lactam antibiotics is production of several beta-lactamase enzymes, which deactivate the beta-lactam antibiotics. In general, a typical beta-lactam antibiotic alone may not be effective in treating infections caused by such beta-lactamase producing bacteria. One alternative to treating infections caused by bacteria producing beta-lactamase enzymes is by co-administration of a beta-lactamase inhibitor with a beta-lactam antibiotic. The beta-lactamase inhibitor prevents deactivation of a beta-lactam antibiotic, typically by binding with the beta-lactamase enzyme. However, even the combination therapy is also proving ineffective in treating infections caused by newer ESBL strains.
Drawz et al. (Clinical Microbiology Reviews, 2010, 23(1), pages 160-201) have reviewed developments in the area of beta-lactamase inhibition and inhibitors. Drawz et al. summarize various beta-lactamase inhibitors developed to overcome bacterial resistance. Gold et al. (The New England Journal of Medicine, 1996, 335(19), pages 1445-1453) have also reviewed the subject of antimicrobial drug resistance.
The widespread emergence of newer strains that do not respond to even the combination therapies, is becoming a major concern. It is estimated that, internationally the prevalence of ESBL in Klebsiella and E. coli is in the range of 30-50% depending upon the geographical location. For ESBLs, carbapenem therapy is the most widely used in the clinical settings today. Presently, all strains identified as inhibitor resistant ESBLs are treated only by carbapenems. However, some of the emerging ESBLs (e.g. those containing metallo-betalactamases, KPCs and Class D ESBLs) appear to exhibit higher degree of resistance to even carbapenems. Thus, there is a need to develop new ways to treat infections that are becoming resistant to known therapies and methods.